Endogenous digoxin-immunoactive factor in human subjects

Endogenous digoxin-like immunoactivity has been detected in the blood of adult patients in renal failure, newborn infants, and pregnant women in the third trimester. Blood levels of this activity increase in pregnant women as gestation progresses, and preliminary data suggest that the activity is increased in hypertensive pregnant women relative to normotensive pregnant women. Similar immunoactivity has also been detected in amniotic fluid and in the urine and serum of normal healthy subjects. The factors giving rise to this immunoactivity cross-react with antibodies used in many commercially available immunoassays for digoxin. The immunoactive factor isolated from human subjects is water soluble and exists tightly but reversibly bound to proteins in serum. The extent of this protein binding is altered in the clinical conditions studied relative to normal adults. This altered protein binding accounts for the detection of this factor by many of the commercially used immunoassays for digoxin. In this article I summarize recent findings related to detecting this activity in the blood of several clinical populations where the accurate measurement of digoxin may be compromised. I also summarize the preliminary isolation and characterization of the factor responsible for this immunoactivity.